Certain 2-(pyridyl-3-thiocarbamoyl-1,3-oxazolidines)



United States Patent 3,546,231 CERTAIN 2-[PYRIDYL-3-THIOCARBAMOYL-1,3-OXAZOLIDINES] George G. King, Guilford, and Joseph V. Karabinos,

Orange, Conn., assignors, by mesne assignments, to 5 The Ansul Company,a corporation of Wisconsin N0 Drawing. Filed May 3, 1968, Ser. No.726,568

Int. Cl. C07d 31/50 U.S. Cl. 260-294.8 4 Claims ABSTRACT OF THEDISCLOSURE Substituted oxazolidines having the formula wherein R isaryl, nitroaryl, haloaryl, alkoxyaryl, pyridyl, alkylenedioxyaryl,cycloaliphatic, hydroxycycloaliphatic, aryloxyalkyl oralkylcarbamoyloxyaryl; R is hydrogen or alkyl; R is alkyl,cycloaliphatic, alkenyl or carbalkoxyalkyl; and X is oxygen or sulfurare prepared by reacting N-(Z-hydroxyethyl)-substituted imines withvarious isocyanates and isothiocyanates. These substituted oxazolidinesare particularly valuable insecticides and herbicides.

wherein R is aryl, nitroaryl, haloaryl, alkoxyaryl, pyridyl,alkylenedioxyaryl, cycloaliphatic, hydroxycycloaliphatic, aryloxyalkylor alkylcarbamoyloxyaryl; R is hydrogen or alkyl; R is alkyl,cycloaliphatic, alkenyl or carbalkoxyalkyl; and X is oxygen or sulfur.

Various oxazolidine derivatives have been previously prepared andreported in the literature. Thus, R. A. Henry et al. in J. Am. Chem.Soc., 71, 22.97 (1949) report derivatives prepared by reactingZ-phenyloxazolidine with phenyl isocyanate and u-naphthyl isocyanaterespectively.

Now it has been found in accordance with this invention thatoxazolidines having substituents in the 2-position and non-arylsubstitution at the carbamoyl nitrogen have valuable biologicalproperties.

The substituted oxazolidines of this invention are prepared by reactingN-(Z-hydroxyethyl)-substituted imines with various isocyanates andisothiocyanates in accordance with the following general equationwherein R, R, R and X are as previously described.

The N-(Z-hydroxyethyl)-substituted imines II employed in the practice ofthis invention are readily prepared by reacting equimolar amounts ofethanolamine with the appropriate aldehydes in refluxing solvent asdescribed by E. D. Bergmann, Chem. Rev. 53, 309 (1953).

Illustrative N-(Z-hydroxyethyl)-substituted imines are 3,546,231Patented Dec. 8, 1970 those compounds H wherein R is phenyl,nitrophenyl, halophenyl, alkoxyphenyl, pyridyl, alkylenedioxyphenyl,cycloaliphatic, hydroxycycloaliphatic or alkylcarbamoyloxyphenyl; and Ris hydrogen or alkyl.

Representatives of these compounds are theN-(2-hydroxyethyl)-benzalamines such as: N-(2-hydroxyethyl)-benzalamine, N (Z-hydroxyethyl)-2-chlorobenzalamine,N-(2-hydroxyethyl)-2,6-dichlorobenzalamine, N(2-hydroxyethyl)-2,4,6-trichlorobenzalamine, N(Z-hydroxyethyl)-2-bromobenzalamine, N(2-hydroxyethyl)-2-fluorobenzalamine, N(2-hydroxyethyl)-4-ioclobenzalamine,N-(Z-hydroxyethyl)-4-nitrobenzalamine, N (2-hydroxyethyl)-2,6-dinitrobenzalamine, N- Z-hydroxyethyl -2,4,6- trinitrobenzalamine,N-(Z-hydroxyethyl)-4ethoxybenzalamine,N-(2-hydroxyethyl)-4-n-butoxybenzalamine, N- (2-hydroxyethyl)-4isopentoxybenzalamine, N (2-hydroxyethyl)-3,4-methylenedioxybenzalamine,N (Z-hydroxyethyl)-3,4 ethylenedioxybenzalamine, N(2-hydroxyethyl)-3,4-n-butylenedioxybenzalamine, N(2-hydroxyethyl)-2-methylcarbamoyloxybenzalamine,N-(2-hydroxyethyl)-3-n-proplycarbamoyloxybenzalamine, N (2-hydroxyethyl)-acetophenone imine, N-(2-hydroxyethyl)-4-chloroacetophenone imine, N-(Z-hydroxyethyl)-propriophenone imine,N-(Z-hydroxyethyl)-4-chloropropriophenone imine andN-(Z-hydroxyethyl)-butyrophenone imine.

Other N-(Z-hydroxyethyl)-substituted imines having the general FormulaII are represented by compounds such asN-(Z-hydroxyethyl)-3-pyridylemethyleneamine, 1-[N-(Z-hydroxyethyl)-acetimidoyl]cyclohexanol, N (2- hydroxyethyl)-2-pyridylmethyleneamine, N (2-hydroxyethyl -4-pyridylemethyleneamine, N-(Z-hydroxyethyl) -3- hydroxy-3-methyl-2-butanone imine,N-(2-hydroxyethyl)- 3-hydroXy-3-methyl-2-pentanone imine,N-(Z-hydroxyethyl)-3-hydroXy-3-ethyI-Z-pentanone imine,N-(2-hydroxyethyl)-3-hydroxy-3-phenyl-2-butanone imine and l- [N-(Z-hydroxyethyl) -acetimidoyl] cyclopentanol.

Preferred N-(Z-hydroxyethyl)-substituted imines include those compoundshaving the Formula II wherein R is halophenyl, pyridyl,alkylenedioxyphenyl wherein the alkylene moiety has 1 to 3 carbon atoms,cycloaliphatic having 4 to 8 carbon atoms, and hydroxycycloaliphatichaving 4 to 8 carbon atoms; and R is hydrogen or lower alkyl, i.e.,alkyl having 1 to 4 carbon atoms.

A variety of isocyanates and isothiocyanates III can be employed in thepreparation of the substituted oxazoli dines of this invention. Thusillustrative isocyanates and isothiocyanates include those compounds HI'wherein R is alkyl. For example, methyl isocyanate, ethyl isocyanate,isopropyl isocyanate, n-pentyl isocyanate, n-octyl isocyanate, dodecylisocyanate and the corresponding isothiocyanates may be suitablyemployed. However, preferred embodiments employ those compounds 111wherein R is lower alkyl, i.e., alkyl having 1 to 4 carbon atoms.

Isocyanates and isothiocyanates having the Formula III wherein R iscycloaliphatic include cyclobutyl isocyanate, cyciopentylisothiocyanate, cyclohexyl isothiocyanate, cyclooctyl isocyanate,cyclododecyl isocyanate, etc. Particularly preferred are thecycloaliphatic compounds III having 4 to 8 carbon atoms in thecycloaliphatic moiety.

Compounds having the Formula HI wherein R is alkenyl include allylisocyanate, allyl isothiocyanate, propenyl isocyanate, butenylisocyanate and pentenyl isocyanate. Preferred are those compoundswherein R is alkenyl having 3 to 5 carbon atoms.

Isocyanates and isothiocyanates III wherein R is carbalkoxyalkyl includeethylisocyanatoacetate, n-propylisocyanatoacetate,n-butylisocyanatoacetate, ethylisocyanatopropionate,methylisocyanatobutyrate, etc Preferred in this class are thosecompounds =III having a total of 3 to 8 carbon atoms.

The substituted oxazolidines I are readily prepared by reacting theN-(2-hydroxyethyl)-substituted imines II with the appropriateisocyanates or isothiocyanates III at a temperature between about C. and140 C. and preferably between about and 80 C.

While the reaction proceeds satisfactorily in the absence of a solvent,inert diluents are preferably employed. Thus, alkanes such as pentane,hexane, etc.; aromatics such as benzene, toluene, xylene; ethers such asethylether, etc. can be suitably employed.

The preparation of the substituted oxazolidines 1 proceedssatisfactorily in the absence of a catalyst. However, catalysts such aspyridine, triethylamine, stannous octoate and triethylenediamine can besuitably employed. While the proportion of catalyst is not critical,generally between about 0.01 and 0.4 mole are employed per mole ofN-(2-hydroxyethyl)-substituted imine II.

The substituted oxazolidines I are obtained in good yield and excellentpurity and are readily isolated by conventional means such asfiltration, recrystallization, and the like.

The compounds I of this invention have a wide variety of usefulapplications. They are particularly valuable in view of their biologicalproperties. Thus, they exhibit strong pesticidal activity asinsecticides and herbicides. Generally, they are mixed with variousadjuvants in these applications, and low concentrations of the compoundare extremely effective.

For example, they are excellent contact insecticides for such insects asthe fly and the Mexican bean beetle. Thus, 2-(o-chlorophenyl) 3methylcarbamoyl-1,3-oxazolidine; 3-methylcarbamoyl 2 (3,4methylenedioxyphenyl) 1,3 oxazoline;2-(3,4-dichlorophenyl)-3-(carbethoxymethylcarbamido) 1,3 oxazolidine;3-methylcarbamoyl-Z-(2-methylcarbamoyloxyphenyl) 1,3 oxazolidine;2-[1-(1-hydroxycyclohexyl)] 2methyl-3-allylthiocarbamoyl-1,3-oxazolidine; 3- (allylthiocarbamoyl)-2,3- pyridyl)-1,3-oxazolidine; 3-(allylthiocarbamoyl)-2 (3,4methylenedioxyphenyl)1,3-oxazolidine and 3-allylthiocarbamoyl 2 (2chlorophenyl)-1,3-oxazolidine were effective in killing flies andMexican bean beetles when applied in an insecticidal solution containing.1% by weight of the insecticide.

The compounds I of this invention are also valuable pre-emergenceherbicides. Thus, 3 methy1carbamoyl-2- (3-nitrophenyl) 1,3 oxazolidine;2-(3',4-dimethoxyphenyl) 3 methylcarbamoyl-1,3-oxazolidine;3-methylthiocarbamoyl 2 (3 nitrophenyl)-1,3-oxazolidine; 3-(N-ethylthiocarbamoyl) 2 [1-(1-hydroxycyclohexy1)]- 2-methy'l 1,3oxazolidine; 2-(2,5-dimethoxypheny1)- 3-methylthiocarbamoyl 1,3oxazolidine and 3-ethylthiocarbamoyl 2 (3,4 methylenedioxyphenyl)-1,3-oxazolidine were effective in controlling mustard and pigweed at a rateof application of 20 pounds per acre.

The post-emergence herbicidal effectiveness of compounds I isillustrated by the control of mustard and pigweed by3-methylthiocarbamoyl 2 (3 pyridyl)- 1,3-oxazolidine;2-(3,4-methylenedioxyphenyl 3 methylthiocarbamoyl 1,3 oxazolidine;2-(2-chlorophenyl)- 3-methylthiocarbamoyl 1,3 oxazolidine; 3(chlorohexylthiocarbamoyl) 2 (3 pyridyl)-1,3-oxazolidine;3-(chlorohexylthiocarbamoyl) 2 (2 chlorophenyl)- 1,3-oxazolidine and 2[1 (1 hydroxycyc1ohexyl)]-2-methyl-3-cyclohexylthiocarbamoyl-1,3-oxazolidine.

The following examples are presented to'illustrate the preparation ofvarious substituted oxazolidines I in accordance with the practice ofthis invention.

EXAMPLE 1 N-(Z-hydroxyethyl) 4 chlorobenzalamine Was prepared byreacting p-chlorobenzaldehyde (28.1 g., 0.20 mole) with ethanolamine(12.2 g., 0.20 mole) in ml. of refluxing ethanol as reported by E. D.Bergmann in Chem. Revs, 53, 309 (1953).

Methyl isocyanate (5.7 g., 0.1 mole) was added drop- Wise to a boiling1:1 hexane-ether solution of N-(2-hydroxyethyl) 4 chlorobenzalamine(18.3 g., 0.1 mole) and 4 ml. of triethylamine. After completion of theaddition, the reaction mixture was refluxed for 4 hours and then allowedto stand overnight. The volatiles were removed by rotary evaporation toprovide 5 g. of a white solid, M.P. 118-20 C. The following analyticaldata revealed that 2-(p-chlorophenyl)-3-methylcarbamoyl-1,3- oxazolidinehad been obtained.

Analysis.Calcd. for C H ClN O (percent): C, 54.89; H, 5.44; N, 11.64.Found (percent): C, 54.72; H, 5.27; N, 11.64.

EXAMPLE 2 EXAMPLE 3 To a well-stirred boiling 1:1 ether-acetone solutionof N-(2-hydroxyethyl)-2,6 dichlorobenzalamine (10.9 g., 0.050 mole)containing 2 ml. pyridine, methyl isocyanate (4.0 g., 0.070 mole) wasadded dropwise. The resulting solution was refluxed for 6 hours. Thefine powdery white solid that separated on standing was collected andair dried to provide 10.4 g. of product; M.P. 151 C. The followinganalytical data revealed that2-(2,6-dichlorophenyl)-3-methylcarbamoyl-1,3 oxazolidine had beenobtained.

Analysis.Calcd. for C H CI N O (percent): C, 48.02; H, 4.40; N, 10.18.Found (percent): C, 47.88; H, 4.46; N, 10.15, 10.27.

EXAMPLE 4 To a boiling ether solution of N-(2-hydroxyethyl)-3-nitrobenzalamine (14.5 g., 0.075 mole) containing 0.1 g.triethylenediamine, methyl isocyanate (5.0 g., 0.087 mole) was addeddropwise. The mixture was refluxed for 6 hours. Upon standing at roomtemperature, a powdery solid separated from the solution. Filtrationprovided 13.2 g. of white solid, M.P. 156-8 C. The following analyticaldata revealed that 3-methylcarbamoyl-2-(3-nitrophenyl)- 1,3-oxazolidinehad been obtained.

Analysis.-Calcd. for C H N O (percent): C, 52.59; H, 5.22; N, 16.73;Found (percent): C, 52.49; H, 5.08; N, 16.86, 16.93.

EXAMPLE 5 To a boiling ether solution of N-(2-hydroxyethyl)-3,4-methylenedioxybenzalamine (19.2 g., 0.10 mole) containin 2 ml. pyridine,methyl isocyanate (7.7 g., 0.13 mole) was added dropwise. The clearsolution was refluxed for 18 hours. Removal of the volatiles on a rotaryevaporator provided 17.5 g. of a clear yellow oil. The followinganalytical data revealed that 3-methylcarbamoyl-2-(3,4-methylenedioxyphenyl) 1,3 oxazolidine had been obtained.

Analysis.-Calcd. for C H N O (percent): C, 57.59; H, 5.64; N, 11.19.Found (percent): C, 57.87; H, 6.04; N, 11.02, 11.03.

EXAMPLE 6 To a boiling 1:1 etherzhexane solution ofN-(Z-hydroxyethyl)-3,4-dichlorobenzalamine (21.8 g., 0.10 mole)containing 2 m1. pyridine, n-butyl isocyanate (9.9 g., 0.10 mole) wasadded dropwise. The solution was refluxed for 6 hours. Removal of thevolatiles gave 23.5 g. of a pale red oil. The following analytical datarevealed that 2-(3,4-

dichlorophenyl) 3 (n-butylcarbamoyl)-l,3-oxazolidine had been obtained.

Analysis.-Calcd. for C14H1BCI2NZO2 (percent): Cl, 22.35; N, 8.83. Found(percent): Cl, 22.58, 22.33; N, 8.87, 8.93.

EXAMPLE 7 To a boiling 1:1 hexane-ether solution ofN-(Z-hydroxyethyl)-3,4-dichlorobenzalamine (21.8 g., 0.10 mole)containing 2 ml. pyridine, ethyl isocyanatoacetate (12.9 g., 0.10 mole)was added dropwise. The clear solution was refluxed for 6 hours. Removalof the volatiles gave 15.2 g. of a pale red oil. The followinganalytical data revealed that 2-(3,4 dichlorophenyl)S-(carbethoxymethylcarbamoyl)-1,3-oxazolidine had been obtained.

Analysis.Calcd. for C H Cl N -O (percent): CI, 20.4; N, 8.07. Found(percent): Cl, 20.1; N, 8.16, 8.21.

cyclohexyl)] 2 methyl 3-methylthiocarbamoyl-1,3- oxazolidine had beenobtained.

Analysis.Calcd. for C H N O S (percent): C, 55.68; H, 8.57; N, 10.82.Found (percent): C, 55.61; H, 8.66; N, 10.85, 11.02.

EXAMPLE 11 Melting Ex. Name of compound point, C. Solvent 12 2-(3,4-dirnethoxyphenyl) -3-methylcarbamoyl-1,3-oxazolidi.ne 13.-3-methylcarbam0y1-2-(2-methylcarbamoyloxyphenyl) -1,3-0xazo1idin 14..2-(p-methoxyphenyl)-3-methylcarbamoyl-1,3-oxazoli dine 15.-Z-(p-chlorophenyl) -3-ethylcarbam0yl-1,3-oxazo1idine 163-(rnethylthiocarbamoyl) -2-(3-nitrophenyl) -1,3-ox azolidine 17--3'methylthiocarbamoyl-2-(3-pyridyl) -1,3-oxazo1idine 182-(3,4-methylenedioxyphenyl) -3-methylthi0carbaJnoyl-l ,3-oxazolidine19-. 2-(2-chloropheuyl) -3-methylthiocarbamoyl-l,3-oxazolidine 20..2-(4-chlor0phenyl) -3-me thylthiocarbamoyl-l,3-oxazolidine 21 -(2,6dichl0rophenyl) -3-methylthiocarbarnoyl-1,3-oxazolidine- 22-(3,4-dichlorophenyl) -3-methylthiocarbamoyl-1,3-oxazolidine 23-(2,5-dimethoxypl1enyl) -3-methylthiocarbamoyll,3-oxazolidiue 242-(2,6-dichlorophenyl) -3-eth ylthiocarbamoyl-1,3-0xazolidine 25 2-(3,4-dichlorophenyl)-3-ethylthiocarbamoyl-1,3-oxazolidine.

26.- 3-ethylthiocarbamoyl-2- (3,4-methylened10xyphenyl) -1,3-oxazol 272-(2-chloropheny1)-3-ethylthiocarbamoyl-1,3-oxazolidine 28.. 3-(eyclohexylthioearbamoyl) -2-(3-pyridyl) -1 ,3-oxazolidine 292-(3,4-dich1or0phenyl) -3-eyclohexylthlocarbamoyl-l,3-0xazolid1ne 30 3(cyclohexylthiocatbamoyl) -2-(2-chlorophenyl) 1,3-oxazolidineg-(allylthiocarbamoyl)-2-(3-pyridyl)-1,3-oxaz0l1d1ne EXAMPLE 8 Anethanol solution of N-(Z-hydroxyethyl) 4-chlorobenzalamine (18.3 g.,0.10 mole) and cyclohexyl isothiocyanate containing 1 ml. pyridine wasrefluxed for 4 hours. Removal of the volatiles on a rotary evaporatorgave 28.5 g. of a light brown oil. The following analytical datarevealed that2-(4-chloropheny1)-3-cyclohexylthiocarbamoyl-1,3*oxazolidine had beenobtained.

Analysis.-Calcd. for C H ClN OS (percent): N, 8.62. Found (percent): N,8.49.

EXAMPLE 9 EXAMPLE 10 An ethanol solution of 7.3 g. (0.10 mole) of methylisothiocyanate, 1 ml. pyridine and 18.5 g. (0.10 mole) of 1 [N-(2hydroxyethyl)acetimidoylJcyclohexanol was heated under reflux for 4 /2hours. Removal of the volatiles on a rotary evaporator provided 15.9 g.of a red oil. The following analytical data revealed that2-[1-(1-hydroxy- What is claimed is: 1. A substituted oxazolidine havingthe ture following strucwherein R is pyridyl, R is hydrogen or loweralkyl, R is lower alkyl, cyclohexyl and allyl and X is sulfur.

2. The compound of claim 1 having the name 3-methylthiocarbamoyl-2- (3-pyridyl) -1,3 -oxazolidine.

3. The compound of claim 1 having the name 3-allylthiocarmaboyl)-2-(3-pyridyl) -1,3-oxazolidine.

4. The compound of claim 1 having the name3-cyclohexylthiocarbamoyl)-2-(3-pyridyl) -1,3-oxazolidine.

References Cited UNITED STATES PATENTS 3,277,105 10/ 1966 Schmidt et al.260295 3,480,640 11/1969 Wilhelm et al. 260-296 ALAN L. ROTMAN, PrimaryExaminer U.S. Cl. X.R.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 546231 December 8 197( George G. King et a1.

It is certified that error appears in the above identified patent andthat said Letters Patent are hereby corrected as shown below:

Column 1, line 63, "R should read R Column 2,

line 21, "proplycarbamoyloxybenzalamine" should readpropylcarbamoyloxybenzalamine line 32, "pyridylemethyleneam: should readpyridylmethyleneamine Signed and sealed this 30th day of March 1971.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. WILLIAM E. SCHUYLER Attesting Officer Commissionerof P:

